Cachexia, Microbiota, Pancreatic Cancer
Conditions
Brief summary
This monocentric study aims at evaluating the effects of fecal microbiota transplantation from newly diagnosed cachectic and non-cachectic pancreatic cancer patients, and healthy volunteers on several cachexia-related parameters of germ-free mice.
Detailed description
Aim: Evaluating the effects of fecal microbiota transplantation (FMT) from 6 newly diagnosed cachectic and 6 non-cachectic pancreatic cancer patients, and 12 healthy age-and sex-matched volunteers on several cachexia-related parameters of 96 germ-free mice (4 per donor) over a 30-day period. The fecal material of all 12 pancreatic cancer patients will be collected at diagnosis before any cancer treatment onset. Hypothesis: FMT of cachectic patients with pancreas cancer, naïve of any anti-cancer treatment and artificial nutrition, into germ-free mice impairs weight gain, in contrast to FMT of non-cachectic patients and healthy controls.
Interventions
None listed
Sponsors
Genton Graf Laurence
Study design
Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Patients with pancreatic cancer (n=12) * ≥18 years and * Newly diagnosed of pancreatic adenocarcinoma (local or metastatic) and * Tube feeding or parenteral nutrition ≤ 14 days Cachectic pancreatic cancer patients (n=6) * Cachexia according to the Fearon criteria 1: involuntary weight loss \>5% over the last 6 months, or any level of weight loss \>2% and a BMI \<20 kg/m2 or sarcopenia. Sarcopenia will be diagnosed by BIA (fat-free mass index is \<17 kg/m2 in men and \<15 kg/m2 in women) 81, and not by CT, as it is faster and can be performed at the bedside of the patient. Non-cachectic pancreatic cancer patients (n=6) * Normal nutritional state: weight stability (± 2% of habitual weight) over the last 6 months, no anorexia before the diagnosis (appetite rating on a visual analogue scale of 100mm), no known impaired glucose tolerance. Healthy matched subjects (n=12) * ≥18 years and * BMI between 18.5 and 30 kg/m2 and * Absence of chronic or acute disease and * Matching for gender and age (± 5 years) with an included pancreatic cancer patient
Exclusion criteria
* \< 18 years or * Inability to give consent or * Insufficient knowledge of project language (French, German) or * Pancreatic adenocarcinoma already treated by chemo- or radiotherapy, or major surgery as duodenopancreatectomy or biliary diversion * Known rheumatologic or immunologic diseases * Therapeutic antibiotics or immunosuppressive drugs (for instance glucocorticoids, cytostatics, antibodies) in the 30 days preceding the inclusion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Body weight changes in mice after fecal material transplantation. | Between days 0 and 30 | Body weight (g) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Body weight | at diagnosis | in kilograms between cachectic patients non-cachectic patients and healthy volunteers |
| Waist-to-hip ratio | at diagnosis | waist circumference (cm) and hip circumference (cm) between cachectic patients non-cachectic patients and healthy volunteers |
| Fat mass | at diagnosis | by bioelectrical impedance analysis (BIA) between cachectic patients non-cachectic patients and healthy volunteers |
| Fat-free mass | at diagnosis | by bioelectrical impedance analysis (BIA) between cachectic patients non-cachectic patients and healthy volunteers |
| Muscle mass | at diagnosis | surfaces of the paraspinal and abdominal wall muscles at the level of L3-L4 disk space by CT for pancreatic cancer patients |
| Nutritional intake | at diagnosis | by 3-day food diary between cachectic patients non-cachectic patients and healthy volunteers |
| Resting energy expenditure (REE) | at diagnosis | by indirect calorimetry between cachectic patients non-cachectic patients and healthy volunteers |
| Appetite | at diagnosis | by visual analogue scale ranging from 0 to 100 mm between cachectic patients non-cachectic patients and healthy volunteers |
| Homeostatic model assessment (HOMA)-score | at diagnosis | by fasting glycemia (mmol/l) and fasting insulinemia (mU/ml)) between cachectic patients non-cachectic patients and healthy volunteers |
| Differences in fecal microbiota | at diagnosis | by 16S rRNA gene amplicon sequencing and functional profiles by metagenomic sequencing between cachectic patients non-cachectic patients and healthy volunteers |
| Insulinemia | at diagnosis | by fasting insulinemia (mU/ml) between cachectic patients non-cachectic patients and healthy volunteers |
| Physical function | at diagnosis | by handgrip strength between cachectic patients non-cachectic patients and healthy volunteers |
| Physical activity | at diagnosis | by the International Physical Activity Questionnaire (IPAQ) between cachectic patients non-cachectic patients and healthy volunteers |
| Quality of life | at diagnosis | by the European Organisation for Research and Treatment of Cancer questionnaire (EORTC QLQ-C30) between cachectic patients non-cachectic patients and healthy volunteers |
| Mortality | at diagnosis | by tumor progression between cachectic patients non-cachectic patients |
| Oral microbiota | at diagnosis | by 16SrRNA gene amplicon sequencing and metagenomic sequencing between cachectic patients non-cachectic patients and healthy volunteers |
| Epithelial permeability | at diagnosis | by fasting levels of plasma zonulin between cachectic patients non-cachectic patients and healthy volunteers |
| GALT function and systemic inflammation | at diagnosis | by fasting plasma level of C-reactive protein (CRP) and cytokines between cachectic patients non-cachectic patients and healthy volunteers |
| Glycemia | at diagnosis | by fasting glycemia (mmol/l) between cachectic patients non-cachectic patients and healthy volunteers |
Countries
Switzerland
Contacts
Primary ContactLaurence Genton Graf, Prof
Backup ContactAlexandra Hemmer, MSc
Outcome results
None listed